EP2292656B1 - Procédé de préparation d'un concentré von Willebrand (fvw) par voie chromatographique et concentré de fvw susceptible d'être ainsi obtenu - Google Patents

Procédé de préparation d'un concentré von Willebrand (fvw) par voie chromatographique et concentré de fvw susceptible d'être ainsi obtenu Download PDF

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Publication number
EP2292656B1
EP2292656B1 EP10186193.8A EP10186193A EP2292656B1 EP 2292656 B1 EP2292656 B1 EP 2292656B1 EP 10186193 A EP10186193 A EP 10186193A EP 2292656 B1 EP2292656 B1 EP 2292656B1
Authority
EP
European Patent Office
Prior art keywords
von willebrand
concentrate
willebrand factor
buffer
fvw
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Not-in-force
Application number
EP10186193.8A
Other languages
German (de)
English (en)
French (fr)
Other versions
EP2292656A2 (fr
EP2292656A3 (fr
Inventor
Serge Martel
Michel Poulle
Sami Chtourou
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
LFB SA
Original Assignee
LABORATOIRE FRANCAIS DU FRACTIONNEMENT ET DES BIOTECHNOLOGIES (Groupement d Interet public)
LFB SA
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Application filed by LABORATOIRE FRANCAIS DU FRACTIONNEMENT ET DES BIOTECHNOLOGIES (Groupement d Interet public), LFB SA filed Critical LABORATOIRE FRANCAIS DU FRACTIONNEMENT ET DES BIOTECHNOLOGIES (Groupement d Interet public)
Priority to PL10186193T priority Critical patent/PL2292656T3/pl
Publication of EP2292656A2 publication Critical patent/EP2292656A2/fr
Publication of EP2292656A3 publication Critical patent/EP2292656A3/fr
Application granted granted Critical
Publication of EP2292656B1 publication Critical patent/EP2292656B1/fr
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Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • C07K14/745—Blood coagulation or fibrinolysis factors
    • C07K14/755—Factors VIII, e.g. factor VIII C (AHF), factor VIII Ag (VWF)
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P7/00—Drugs for disorders of the blood or the extracellular fluid
    • A61P7/04—Antihaemorrhagics; Procoagulants; Haemostatic agents; Antifibrinolytic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides

Definitions

  • the present application relates to a process for the preparation of a von Willebrand factor concentrate (VWF) by chromatographic means and a FvW concentrate which can thus be obtained.
  • VWF von Willebrand factor concentrate
  • Von Willebrand factor is a multimeric blood protein with molecular weights ranging from about 200 kDa to about 20,000 kDa or more.
  • This protein synthesized by platelets and endothelial cells, plays a key role in the fight against blood bleeding insofar as vWF acts as a gellable buffer that spreads over a vascular breach providing platelet adhesion for perform the first phase of hemostasis, namely the formation of the "platelet nail" (thrombus). Around this thrombus will organize the coagulation phenomena intended to consolidate the cessation of bleeding by formation of an insoluble fibrin clot.
  • VWF also provides stabilization and transport of Factor VIII in the bloodstream, to which it is associated in the form of complexes of varying sizes, which is thus protected against rapid degradation by proteolysis due to the sensitivity of isolated Factor VIII to proteases.
  • vWF human plasma derivatives enriched in vWF of very high purity compatible with multiple and repeated injections.
  • insufficiently purified samples of vWF from human plasma fractionation contain various contaminants (residual proteins) that can induce undesirable immunological responses.
  • the administration of von Willebrand factor Factor VIII may result in a risk of thrombosis or hypercoagulability for the treated patient ( Makris et al, Thromb.Haemost, 88, 2002, pp.377-378 , Manucci PM, Thromb.Haemost, 88, 2002, pp.378-379 ).
  • VWF concentrates typically involve steps of precipitation of a plasma fraction, intended for the removal of most of the unwanted proteins (fibrinogen, fibronectin etc.), and / or chromatographies (exchange of ions, affinity, immunoaffinity, steric exclusion etc.) which aim to obtain very high purity concentrates with a high specific activity, and which make it possible to preserve the integrity of the multimeric forms, especially those high molecular weight whose biological importance is fundamental in the healing processes.
  • chromatographies exchange of ions, affinity, immunoaffinity, steric exclusion etc.
  • the flow rate is reduced to the value of that of step a) and the elution of the VWF (step d)) is carried out by using the buffer of step a) whose ionic strength is increased.
  • This increase in the ionic strength is advantageously carried out by adding sodium chloride, the final concentration of which is brought to 0.15-0.17 M.
  • the use according to the invention of the vinyl polymer matrix chromatographic support according to the invention of a slightly hydrophobic nature, allows the separation of VWF from impurities and / or accompanying proteins, such as fibronectin.
  • the VWF obtained by the method is also devoid of Factor VIII.
  • the implementation of the method after the ultrafiltration step, leads to a highly purified, therapeutic grade, vWF concentrate having a specific activity (A.S.) of at least 90 IU RCo / mg protein.
  • the ratio R representing Factor VIII: C / FvW: RCo, is less than 0.06%. This result reveals that FvW concentrate lacks Factor VIII or contains only minute doses.
  • Table 4 shows the content of various proteins present in a lyophilized and dry-heated fraction of vWF dissolved again in 10 ml of PPI water, obtained according to the process of the invention (Product III) and according to Method A ( Product IV). The values given represent the average values of three tests.

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Organic Chemistry (AREA)
  • Medicinal Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Hematology (AREA)
  • Zoology (AREA)
  • Toxicology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Molecular Biology (AREA)
  • Genetics & Genomics (AREA)
  • Biophysics (AREA)
  • Biochemistry (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Diabetes (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Chemical & Material Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Peptides Or Proteins (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
EP10186193.8A 2004-08-16 2005-07-20 Procédé de préparation d'un concentré von Willebrand (fvw) par voie chromatographique et concentré de fvw susceptible d'être ainsi obtenu Not-in-force EP2292656B1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
PL10186193T PL2292656T3 (pl) 2004-08-16 2005-07-20 Sposób wytwarzania koncentratu czynnika von Willebranda (FvW) poprzez chromatografię i koncentrat czynnika von Willebranda, który może być uzyskany zgodnie ze wspomnianym sposobem

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
FR0408897A FR2874216B1 (fr) 2004-08-16 2004-08-16 Procede de preparation d'un concentre de facteur von willebrand (fvw) par voie chromatographique et concentre de fvw susceptible d'etre ainsi obtenu
EP05291553.5A EP1632501B1 (fr) 2004-08-16 2005-07-20 Procédé de préparation d'un concentré de facteur von Willebrand (FvW) par voie chromatographique et concentré de FvW susceptible d'être ainsi obtenu

Related Parent Applications (2)

Application Number Title Priority Date Filing Date
EP05291553.5A Division EP1632501B1 (fr) 2004-08-16 2005-07-20 Procédé de préparation d'un concentré de facteur von Willebrand (FvW) par voie chromatographique et concentré de FvW susceptible d'être ainsi obtenu
EP05291553.5 Division 2005-07-20

Publications (3)

Publication Number Publication Date
EP2292656A2 EP2292656A2 (fr) 2011-03-09
EP2292656A3 EP2292656A3 (fr) 2012-01-25
EP2292656B1 true EP2292656B1 (fr) 2014-05-21

Family

ID=34948021

Family Applications (2)

Application Number Title Priority Date Filing Date
EP05291553.5A Not-in-force EP1632501B1 (fr) 2004-08-16 2005-07-20 Procédé de préparation d'un concentré de facteur von Willebrand (FvW) par voie chromatographique et concentré de FvW susceptible d'être ainsi obtenu
EP10186193.8A Not-in-force EP2292656B1 (fr) 2004-08-16 2005-07-20 Procédé de préparation d'un concentré von Willebrand (fvw) par voie chromatographique et concentré de fvw susceptible d'être ainsi obtenu

Family Applications Before (1)

Application Number Title Priority Date Filing Date
EP05291553.5A Not-in-force EP1632501B1 (fr) 2004-08-16 2005-07-20 Procédé de préparation d'un concentré de facteur von Willebrand (FvW) par voie chromatographique et concentré de FvW susceptible d'être ainsi obtenu

Country Status (10)

Country Link
US (1) US7888476B2 (es)
EP (2) EP1632501B1 (es)
JP (1) JP4822765B2 (es)
AU (1) AU2005203243A1 (es)
BR (1) BRPI0503183A (es)
CA (1) CA2514438A1 (es)
DK (2) DK2292656T3 (es)
ES (2) ES2450967T3 (es)
FR (1) FR2874216B1 (es)
PL (2) PL1632501T3 (es)

Families Citing this family (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
FR2920429B1 (fr) * 2007-08-30 2012-10-05 Lfb Biotechnologies Procede de purification du facteur viii et du facteur von willebrand
CN105816858A (zh) * 2007-12-28 2016-08-03 巴克斯特国际公司 重组vwf配方
US11197916B2 (en) 2007-12-28 2021-12-14 Takeda Pharmaceutical Company Limited Lyophilized recombinant VWF formulations
ES2298096B1 (es) * 2008-01-08 2009-01-01 Grifols, S.A. Procedimiento para la obtencion de un concentrado de factor von willebrand o del complejo de factor viii/factor von willebrand y utilizacionde los mismos.
EP2326658A4 (en) * 2008-09-12 2013-04-10 Ge Healthcare Bio Sciences Ab IMPROVED PROTEIN-AGGREGATE SEPARATION WITH MULTIMODAL ANION EXCHANGERS IN THE PRESENCE OF ZWITTERIONS EXCLUDED FROM THE PROTEIN
CN102387784B (zh) * 2008-10-21 2014-04-02 巴克斯特国际公司 冻干的重组vwf配方
IT1396528B1 (it) 2009-01-19 2012-12-14 Kedrion Spa Nuovo processo di purificazione altamente selettivo di due proteine plasmatiche: von willebrand factor (vwf) e fibronectina (fn).
WO2012082933A1 (en) 2010-12-15 2012-06-21 Baxter International, Inc. Eluate collection using conductivity gradient
WO2019038350A1 (en) 2017-08-23 2019-02-28 Csl Behring Gmbh PROCESS FOR VIRAL FILTERING OF VON WILLEBRAND FACTOR

Family Cites Families (13)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4342748A (en) * 1980-07-08 1982-08-03 President And Fellows Of Harvard College Sleep-promoting factor
FR2632309B1 (fr) 1988-06-07 1990-08-24 Lille Transfusion Sanguine Procede de purification par voie chromatographique de proteines, notamment de facteur viii, et les produits obtenus
DE3904354A1 (de) 1989-02-14 1990-08-16 Behringwerke Ag Pasteurisiertes, gereinigtes von willebrand-faktor-konzentrat und verfahren zu seiner herstellung
FR2665449B1 (fr) * 1990-08-02 1995-04-14 Aquitaine Developp Transf Sang Procede de fabrication de facteur von willebrand ayant une tres haute purete, depourvu en majeure partie de facteur antihemophilique (fviiic), et facteur von willebrand ainsi obtenu, ainsi qu'une composition pharmaceutique le contenant.
FR2651437A1 (fr) * 1989-09-05 1991-03-08 Lille Transfusion Sanguine Procede de preparation de concentre du complexe facteur viii-facteur von willebrand de la coagulation sanguine a partir de plasma total.
FR2673632A1 (fr) * 1991-03-08 1992-09-11 Lille Transfusion Sanguine Procede de preparation de concentre de facteur von willebrand humain de tres haute purete, approprie a un usage therapeutique.
DE4204694C3 (de) * 1992-02-01 1995-10-12 Octapharma Ag Verfahren zur Gewinnung von hochreinem, virusinaktiviertem Faktor VIII mittels Anionenaustauscher-Chromatographie
US6518482B2 (en) 1994-09-13 2003-02-11 American National Red Cross Transgenic non-human mammals expressing human coagulation factor VIII and von Willebrand factor
DE4435485C1 (de) * 1994-10-04 1996-03-21 Immuno Ag Verfahren zur Gewinnung von hochreinem von Willebrand-Faktor
AT406867B (de) 1997-02-27 2000-10-25 Immuno Ag Verfahren zur gewinnung von hochreinem vwf oder faktor viii/vwf-komplex
AT405403B (de) * 1997-02-27 1999-08-25 Immuno Ag Reinigung von von willebrand-faktor durch kationenaustauscherchromatographie
US6531577B1 (en) 1997-12-15 2003-03-11 Hemasure Denmark A/S von Willebrand factor (vWF)-containing preparation, process for preparing vWF-containing preparations, and use of such preparations
FR2857267B1 (fr) 2003-07-09 2006-03-10 Lab Francais Du Fractionnement Formulation stabilisante et solubilisante pour les proteines cryoprecipitables.

Also Published As

Publication number Publication date
CA2514438A1 (fr) 2006-02-16
US20060036081A1 (en) 2006-02-16
PL2292656T3 (pl) 2014-09-30
ES2450967T3 (es) 2014-03-25
FR2874216B1 (fr) 2006-11-03
EP2292656A2 (fr) 2011-03-09
EP1632501A1 (fr) 2006-03-08
DK1632501T3 (en) 2014-03-03
JP4822765B2 (ja) 2011-11-24
PL1632501T3 (pl) 2014-05-30
DK2292656T3 (da) 2014-07-28
AU2005203243A1 (en) 2006-03-02
EP2292656A3 (fr) 2012-01-25
FR2874216A1 (fr) 2006-02-17
US7888476B2 (en) 2011-02-15
BRPI0503183A (pt) 2006-05-16
JP2006058298A (ja) 2006-03-02
ES2483151T3 (es) 2014-08-05
EP1632501B1 (fr) 2013-12-25

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